Leiomyomas or "fibroids" are smooth muscle tumors that occur commonly in the uterine wall and less frequently in the intestinal wall. It is estimated that roughly 10 percent of all women of childbearing age develop these tumors (between 10 and 15 million women) in the U.S. The major goal of this project is to use recombinant DNA techniques to clone and characterize one of the genes that appear to play a major role in the formation of leiomyomas. In a large proportion of leiomyomas, a frequently observed chromosomal abnormality is the balanced, non-random translocation involving chromosomes 12 and 14 [t(12;14)(q14-15--q24)]. Although other chromosomal alterations ( such as deletions in chromosome 7q) are also seen, the t(12;14) translocation has been described in many leiomyomas as the only observable cytogenetic abnormality, suggesting that the gene or genes interrupted by this translocation might play a major role in the formation or progression of this tumor. We have recently identified flanking markers that bracket the leiomyoma t(12;14) translocation breakpoint to a small region on chromosome 14. Our studies have placed the translocation breakpoint between the markers D14S277 and UT601, a genetic distance of zero centimorgans. Using these markers as probes, we have identified YAC clones that span the translocation breakpoint based on FISH analysis of translocated chromosomes. The YAC clones will be used to isolate cosmid and cDNA clones which will be mapped with respect to the translocation breakpoint using in situ hybridization and pulsed field gel electrophoresis. DNA clones that detect or are directly interrupted by the translocation will be scanned for expressed sequences such as "exon trapping", scanning for CpG rich sequences, and sequences that are conserved between different species. The gene or genes identified in this manner will be characterized with respect to differences in structure or expression in the tumors as well as the tissue distribution and sub cellular localization of their products in normal smooth muscle cells and tumors.